Carbohydrate c-nitroolefins and method of preparation



Patented Nov. 14, 1950 PATENT OFFICE r CARBOHYDRATE C-NITROOLEFINS AND METHOD OF PREPARATION Y John Clinton Sowden, St. Louis, Mo., assignor to Corn Products Refining Company, New York,

N. Y., a, corporation of New Jersey No Drawing. Application August 29, 1947, Serial No. 771,377

4, 21 Claims. 1

This invention relates, generally, to the produc- -tion of (1) the 'acetylated nitroolefins, (2) the acetylated didesoxynitroalcohols, and (3) the '2-desoxy aldoses of unsubstitutedaldose sugars.

An important object of the invention is the provision of new and'improved methods of producing the above mentioned derivatives of unsubstituted aldose sugars.

' Another important object of the invention is the provision of the acetylated nitroolefins derived from unsubstituted aldose sugars, as new compositions of matter.

Still another important object of the invention is the provision of the acetylated didesoxynitroalcohols derived from unsubstituted aldose sugars,

as new compositions of matter.

Certain other objects of the invention will, in

' part, be obvious, and will, in part, appear hereinafter.

The following synthesis of D-arabo-2 desoxyhexose (2-desoxyglucose) from D-arabinose will serve to illustrate the broad aspects of the inven- -'tion:

OHzNOg ,CHQNOZ CHO I I "H OH H H HooH 1 g CHaNOz Ho H Ho H A020 H OH .OHaONa H OH H OH NaHGO;

H OH

H OH H OH HzOH H2OH oH'ioH I II III oHNO, oHiNoi CHO H H, OH: 'AcOH Hi AoOGH NaOH Ho H H60 Pd H OAc H2804 H OH H OAc H 0A0 H OH H1010 H2010 HQOH iv v v:

. D-arabinose, I, is condensed with nitromethane the-presence of sodium'methoxide to form the stereo-isomeric nitroalcohols, l-nitro-l-desoxy- -D-sorbitol, II, and l-nitro-l-desoxy-D-mannitol,

III. A detailed discussion ofthe preparation of these and other carbohydrate C-nitroalcohols is tion, are acetylated in known manner with acetic anhydride containing acatalytic amount of sulfuric acid so as to form the pentaacetates of II and III. These pentaacetatesare refluxed with sodium bicarbonate in dry benzene to form D- arabo-tetraacetoxy-l-nitrohexene-l, IV. It will be noted that only one acetylated nitroolefin, IV, is formed in this reaction, sincethe formation 5 of the double bond destroys the asymmetry of the second carbon atom of the acetylated nitroalcohols, II and III.

When the acetylated nitroolefin, IV, from D- arabinose is reduced in absolute alcohol with hy- 1 =drogen and palladium black, one mole of hydrogen is rapidly taken up by the double bond, whereas theensuing reduction of the nitro-group is much slower. By interrupting the reduction after the absorption of the first mole of hydrogen, it is possible to isolate the acetylated 1,2-didesoxynitroalcohol, V, in good yield. When this latter substance is deacetylated with excess aqueous alkali, and the resulting solution of sodium nitroalcohol is added to moderately concentrated sulfuric acid, D-arabo-Z-desoxyhexose, VI, (the name used here for this desoxy sugar follows the nomenclature'proposed by'SoWden, Journal of the American Chemical Society, 69, 1047 (1947)) can be isolated from the resulting solution as its .25 benzylphenylhydrazone in 70 percent yield.

OHBNOQ AcO H H OAc HzOAc I-nitro 1 desoxy-D-mannitol pentaacetate (VII) CHO HC JOAc HzOAc 1-Xylo-tetraacetoxy l-nitrohexene-1 (VIE) CHz'OH H OH HOCH 1 H 3oH HooH HzNOz 6-.nitro 6-desoxy-D-!sorbit0l (IX) CHNOz H HC OAc H OAc H OAc HQOAc D gluco-pentaacetoxy-1-nitroheptene-1 (X) CH2NO7 H on H OH

HfJOH Eton 1 nitro- 1 -desoxy-D- -glucoheptitol XI) The nitroiilefins and acetylated nitroiilefins, described herein, have been given systematic names as derivatives of the corresponding aliphatic olefins, using the appropriate prefix to signify their carbohydrate configuration. Thus, IV, is named D-arabo-tetraacetoxy-1-nitrohexene-l. The nitroolefins as a class may be designated as polyhydroxyalkyl-l-nitroalkenes and the acetylated nitroolefins as polyacetoxy-lnitro-l-alkenes. The didesoxynitroalcohols as a class may be designated as 2-polyhydroxyalkyll-nitroalkanes and the acetylated didesoxynitroalcohols as 2-polyacetoxyalkyl-1-nitroalkanes.

I have found that the synthesis and reactions outlined above, starting with D-arabinose, I, as illustrative, are applicable, generally, to unsubstituted aldose sugars. In each instance, the corresponding acetylated carbohydrate C-nitroiilefins have been obtained in crystalline condition and in good yield. These acetylated carbohydrate C-nitroiilefins were found to crystallize with extreme ease, even from solutions containing large amounts of other acetylated carbohydrate material.

The acetylated carbohydrate C-nitroiilefins ma be readily reduced catalytically to the corresponding acetylated 1,2-didesoxynitroalcohols. These latter substances may be readily converted to the corresponding z-desoxyaldoses by deacetylation followed by removal of the nitrogroup by treatment with sulfuric acid. The yields are generally good throughout the synthesis.

The following examples, which are intended as informative and typical only and not in a limiting sense, will further illustrate the invention, which is intended to be limited only in accordance with the scope of the appended claims.

I-nitro 1 desoxy-D-mannitol pentaacetate (VII) .Three grams of l-nitro-l-desoxy-D- mannitol (Sowden and Fischer, Journal of the American Chemical Society, 66, 1312' (1944)) was acetylated on the steam bath for one-half hour with 20 cc. of acetic anhydride containing one drop of sulfuric acid. After cooling, the solution was poured onto ice and water and there resulted 5.26 g. (88%) of the crystalline pentaacetate. After recrystallization from a mixture of ether and petroleum ether, the product melted at 88 to 89 C. and showed +B7.8 in absolute chloroform, c 7.3. Anal. Calcd. for

appear after a few minutes.

4 C1eH2aO12N (421.3); C, 45.6; H, 5.50. Found: C, 45.7; H, 5.53.

Neither pyridine nor sodium acetate were found to be satisfactory acetylation catalysts for the nitroalcohol, both yielding dark colored sirups.

D arabo-tetraacetoccy-l-nitrohexene-1 (IV). From the nitroalcohol pentaacetate.ne gram of 1-nitro-1-desoxy-D-mannitol pentaacetate in 20 cc. of dry benzene was refluxed for 2 hours with 1 g. of sodium bicarbonate. The mixture was cooled, filtered and concentrated to dryness. The resulting crystalline residue on recrystallization from a mixture of ether and petroleum ether yielded 0.74 g. (86%) of the acetylated nitroolefin. The pure product melted at 115 to 116 C. and showed +32.4 in absolute chloroform, c 5.2. Anal. Calcd. for C14H19O10N' (361.3): C, 46.5; H, 5.30. Found: 0, 16.4; H, 523.

Example 2 D arabo tetmacetoxy-Imitrohexene (IV). From D-arabinose.A suspension of g. of D- arabinose in 50 cc. of absolute methanol and 50 cc. of nitromethane was shaken with 75 cc. of methanol containing 2.1 g. of sodium. The sugar-dissolved rapidly and an amorphous precipitate of the sodium nitroalcohols began to After shaking for hours,-the mixture was diluted with 60 cc. of dry ether and the precipitate was filtered and washed successively with cold methanol, ether and petroleum ether. After drying over phosphorus pentoxide, the light colored powder weighed 153- g. and contained 9.05% of sodium. The powder was dissolved in 100 cc. of water and immediately passed through a column containing a cation-exchange resin operating on the hydrogen cycle. These synthetic ion-exchange materials are phenol-formaldehyde, sulfonic acidv derivatives and are described in the following paper and elsewhere in the literature: Adams & Holmes, Journal Soc. Chem. Ind., 54, 1-6T (1935). Concentration of the eflluent at reduced pressure and thorough drying over phosphorus pentoxide yielded 11 g. of light yellow sirup. Acetylation of this sirup on the steam bath for one hour with 120 cc, of acetic anhydride containing one drop of sulfuric acid yielded 20 g. of the sir'upy acetates. Treatment of this sirup in 250cc. of benzene with 20 g. of sodium bicarbonate, as described above, followed by concentration of the resulting filtered solution then gave 9.7 g. (40%) of the acetylated nitroiilefin. After recrystallization from absolute ethanol, the product melted at 115 to 116 C.

Example 3 L- -xylo-tetraacetoxy-lmitrohexened (VIII). From fi-nitro-fi-desozcysorbitol (IX) .-Ten grams of the nitroalcohol (Sowden and Fischer, Journal of the American Chemical Society, 6'7, 1713 (1945)) were acetylated for 24 hours at room temperature with cc. of acetic anhydride toms. ear r A -fiat. Galedfor; QiiHmQmNi 3351' 3): -55. 5-..30; 388i; Bound; 6;. fi th. 55%;; $13-$93.

' v Enameled 'I. a 123110 tetumcetowyebnitrohezrencel m L=$HZQ$6; WHQIL 7- g... Q ;L -xy1ose pr pm fmm 2,g1 .-ben,zy1idene sorbitol by, the method. oi v. Vargha, Ber., 68, 18 (1935)) was treatedexactly asdescribed above-mlelxample 2,.for, Q-arabinose,

therewas obtained; 3.55?- gi. (21%). of. the, crystal:- line acetylated nitrolefi'm. After. crystallization. from. absolute. ethanol. t e. product; melted at; 1.15. to. .116." C.

lwamrlei D glfuco-pentaccetowg-I nitroheptene-i (*X')-. From 1 nitro 1 desoary-D- -glucoheptitol XL)*-.--Acetylation of 1: g. of l -nitro-l' -desoxyfi m-glucoheptitol (Sowd'enand- Fischer; Journal' of the American- Chemical Society, 68, 1511, (1946)) with acetic anhydride and sulfuric acid yielded 1.54 g. (-75-%)- of the: crude, crystalline hexaacetate, M; P. '72-to-75 C. The=hexaacetate contained a smallamount. of'theacety1ated='nitroiilefin, M. P. 1:96 to 107- C., described below, and: purification by:- recrystallization was found to. be very difficult. Accordingly, the crude mar terial was converted directly to the acetylated nitroiilefin. by treatment inv benzene solutionwith sodium bicarbonate. The product, obtained in 81 percent yield from the hexaacetate, was recrystallized from absolute ethanol and then melted at 106 to 107 C. and showed +18 in absolute chloroform; c 4.2.. Anal. Calcd. for C1'1H23O12N (433.4): C, 47.1; H, 5.35; 3.23: und Q, ii-8;. .12;: 3.57..

Example 6 D xylo-tetraacetoxy-I -m'trohexene-1 Ten rams of ly-xylose, when treated, as described above in Example 2 for D-arabinose, yielded. &-.45 g (35%). of the corresponding. acetylated. nitroolefin. After recrystallization teem, absolute ethanolthe product melted at 1115 .to-1 16 C. and showed +1O.2 in absolute chloroform, Anal. Calcd. for C14H19010N= (361.3): C, 46.5; H, 5.30; N. 3.88. Found: C, 46.5; H, 5.30; N, 3.80.

Example 7 D-ribo-tetraacetozcil-I-nitrohexene-1. Ten r grams of D-ribose, when treated, as described above in Example 2 for D-arabinose, yielded 5.15 g. (21%) of the corresponding acetylated nitroolefin. Recrystallized from absolute ethanol, the product melted at 86 to 87 C. and showed +17 in absolute chloroform, :c 5. Anal. Calcd. for C14H19010N (361.3): C, 46.5; H, 5.30; N, 3.88. Found: C, 46.5; H, 5.28; N, 3.87.

Unlike the acetylated nitroiilefins described above, which were all very pale yellow in color, the product from D-ribose was colorless.

Example 8 1-nz'tr0-1, 2-dides0:cy-D-arab0hea:itol tetraacetate (V) .-Two grams of the acetylated nitroiilefin, IV, Example 1, in 20 cc. of absolute ethanol were shaken with hydrogen at room temperature and pressure in the presence of 0.2 g. of palladium black following the technique described by Tausz and Putnoky, Ber., 52, 1573 (1919). One mole of hydrogen was absorbed in 12 minutesandthe rate of reduction then dropped sharply. Concentration and cooling of the filtered solution yielded 1.58 g. (79%) of the acetylated didesoxynitroal- Example. 9,

D arabo-Z-dcsox-yhexose; z-descxyglucose" (VI)*)".-0ne gram oft-he crude acetylated dielesoioynitroalcohol M. P: 8% to- 86* 6., described above in Example 8', was dissolved at room temperature in- 15 cc; 1 normal sodium hydroxide solution and allowed to stand for one hour. I The sol-utionwasthen added toa stirred mixture of 3 cc. of waterand' 2.1" cc. of sulfuric" acid at room temperature. The solution was diluted and neutra'lized' by stirring with barium carbonate. After centrifuging and filtering, thesolution was treated with a fewdrops of acetic andwa-s concentrated to-dryness at reduced pressure; Treatment of the resultingsirup with 0:.6cc. of benzyl phenylhydrazine in 10 cc. of percent ethanolthen yielded 0.6 g. (71%) ofD-arabo-Z-desoxyhexose benzylphenylhydrazone.

After recrystallization from ethyl acetate; the hydrazone melted at 158 to 159 C. and showed +7.6 in methanol; 01.2. Gleava-ge of the hydirazone with benzaldehyde according to the directions of Berg-mann, Schotte and Lechinsky, B612, 55}, 158 (1922) gave the crystalline D arabo 2-desoxyhexose;

(1- hour) in Water, 02-5 v The desoxy sugarapparently was obtained as a.- minture predominating inthe" -form since its initial 'melting point of 128 to 129 C. was lowered to 123 to C. on recrystallization and? a slight downward mutarotati'on was: evident in its aqueous solution: 25+53=.8, 10' minutesj +5037; 2(T-minutes; +48 30 minutes;- +46.-6--, 1 hour (constant).

the above: examples; the acetylated carboelse-.3.

i hydrate C nitroalcohols have been treated with sodium bicarbonateinbenzene to give the corresponding acetylated nitrodlefins. In this treatment, the sodium bicarbonate may be replaced with another alkali metal bicarbonate, such as potassium bicarbonate. The benzene takes no part in the treatment but serves as a suspension medium for the reactants. Hence, it may be replaced with other compounds, such as nitrobenzene, ether, chloroform, methanol, ethanol, etc.

I claim:

1. The process of making polyacetoxy-lnitro-l-alkenes which comprises acetylating 1- nitro-l-desoxyalditols and effecting chemical reaction between the resulting acetylated compounds and an alkali metal bicarbonate by refluxing in dry benzene.

2. The process of making 2-polyacetoxyalkyll-nitroalkanes which comprises catalytically reducing polyacetoxy-1-nitro-1-a1kenes.

3. The process of making 2-desoxyaldoses which comprises deacetylating 2-polyacetoxyalkyl-l-nitroalkanes and removing the nitro group from the resulting 2-polyhydroxyalkyl-1- nitroalkanes by hydrolysis thereof.

4. The process of making 2-polyacetoxyalkyll-nitrolakanes which comprises acetylating 1- nitro-l-desoxyalditols, efiecting chemical reaction between the resulting acetylated compounds and an alkali metal bicarbonate by refluxing in dry benzene thereby forming polyacetoxy-l-nitro-l-alkenes and catalytically reducing the resultant polyacetoxy-l-nitro-1-alkenes.

5. The process of making Z-desoxyaldoses which comprises acetylating l-nitro-l-desoxyalditol, effecting chemical reaction betweenthe resulting acetylated compound and analkali metal bicarbonate by refluxing in dry benzene thereby forming polyacetoxy-l-nitro-l-alkene, catalytically reducing the resultant polyacetoxy-l-nitro-l-alkene, deacetylating the resultant 2-polyacetoxyalkyl-l-nitroalkane, and removing the nitro group from the resultant 2-polyhydroxyalkyl-1- nitroalkane. 1 6. The process of claim 1 wherein the acetylated 1-nitro-1-desoxyaldito1s" are refluxed with sodium bicarbonate in dry benzene. 7. The process of claim 3 wherein the 2-p0ly acetoxyalkyl-1-nitroalkanes are deacetylated by dissolution in alkali metal hydroxide, followed by acidification with sulfuric acid, neutralization by an alkaline earth metal carbonate, filtration. treatment with benzylphenylhydrazine and cleavage with benzaldehyde.

8. As a new composition of matter polyacetoxyl-nitro-l-alkene. 9. As a new composition of matter 2-polyacetoxyalkyl-l-nitroalkane.

10. The process of claim 1 wherein acetic anhydride containing a catalytic amount of sulv 13. As' a new composition of matter l-nitro-l,

2-didesoxy-D-arabohexitol tetraacetate.

14. As a new composition of matter D-glucopentaacetoxy-l-nitroheptene-1. 15. The process of making D-gluco-pentaacetoxy-l-nitroheptene-l which comprises,acetylat-' ing l-nitro l-desoxy-D- -glucoheptitol, and

8 subjecting" the resulting acetylated nitroalcohol to treatment'with-an alkali metal bicarbonate. I

16. The process of claim 15 wherein the acetylating medium is acetic anhydride containing a catalytic amount of sulfuricacid. r 17. The process of claim 15 wherein the resultant acetylated l-nitro-l-desoxy-D- fl-glucoheptitol is refluxed with sodium bicarbonate in dry benzene.

18. The process of making D-arabo-2-desoxyhexose which comprises dissolving 1 nitro 1,2- diciesoxy-D-arabohexitol tetraacetate in alkali metal hydroxide, followed by acidificationwith sulfuric acid, neutralization by an alkaline-earth metal carbonate, filtration, treatment with benzylphenylhydrazine, and cleavage with benzaldehyde. 4

19. The process of making D arabo-tetraacetoxy-l-nitrohexene-l which comprises acetylating at least one carbohydrate C-nitroalcohol selected from the group consisting of l-nitro-l-desoxy-D-sorbitol and l-nitro-l-desoxy-D-mannitol, and subjecting the resulting acetylated nitroalcohol to treatment with an alkali metal bicarbonate by refluxing in dry benzene.

20. The process of claim 19 wherein the acetylating medium is acetic anhydride containing a catalytic amount of sulfuric acid.

21. As a new composition of matter D-arabodesoxyacetoxy-l-nitrohexene-1.

JOHN CLINTON SOWDEN.

REFERENCES CITED The following reierences are of record in the file 'of this patent: 

18. THE PROCESS OF MAKING D-ARABO-2-DESOXYHEXOSE WHICH COMPRISES DISSOLVING 1 - NTIRO - 1,2DIDESOXY-D-ARABOHEXITOL TETRAACETATE IN ALKALI MATAL HYDROXIDE, FOLLOWED BY ACIDIFICATION WITH SULFURIC ACID, NEUTRALIZATION BY AN ALKALINE-EARTH METAL CARBONATE, FILTRATION, TREATMENT WITH BENZYLPHENYLHYDRAZINE, AND CLEAVAGE WITH BENZALDEHYDE.
 21. AS A NEW COMPOSITION OF MATTER D-ARABODESOXYACETOXY-1-NTIROHEXENE-1. 